Vibrational spectroscopic and molecular docking study of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide

Article abstract of DOI:10.1016/j.saa.2015.06.083

FT-IR and FT-Raman spectra of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide were recorded and analyzed experimentally and theoretically. The synthesis, ¹H NMR and PES scan results are also discussed. Nonlinear optical behavior of the examined molecule was investigated by the determination of first hyperpolarizability. The calculated HOMO and LUMO energies show the chemical activity of the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. From the MEP it is evident that the negative charge covers the carbonyl group and the positive region is over the NH group. The calculated geometrical parameters (SDD) are in agreement with that of similar derivatives. Molecular docking simulations against targets from Mycobacterium tuberculosis are reported and the results suggest that the compound might exhibit inhibitory activity against PknB.

Full text of DOI:10.1016/j.saa.2015.06.083

Accepted Manuscript
Vibrational spectroscopic and molecular docking study of (2E)-N-(4-chloro-2-
oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide
Rajeev T. Ulahannan, C. Yohannan Panicker, Hema Tresa Varghese, Robert
Musiol, Josef Jampilek, Christian Van Alsenoy, Javeed Ahmad War, Abdulaziz
A. Al-Saadi
PII:
S1386-1425(15)30013-5
http://dx.doi.org/10.1016/j.saa.2015.06.083
SAA 13853
DOI:
Reference:
To appear in:
Spectrochimica Acta Part A: Molecular and Biomo-
lecular Spectroscopy
Received Date:
Revised Date:
Accepted Date:
10 November 2014
20 June 2015
22 June 2015
Please cite this article as: R.T. Ulahannan, C. Yohannan Panicker, H.T. Varghese, R. Musiol, J. Jampilek, C.V.
Alsenoy, J.A. War, A.A. Al-Saadi, Vibrational spectroscopic and molecular docking study of (2E)-N-(4-chloro-2-
oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide, Spectrochimica Acta Part A: Molecular and Biomolecular
Spectroscopy (2015), doi: http://dx.doi.org/10.1016/j.saa.2015.06.083
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Vibrational spectroscopic and molecular docking study of (2E)-N-(4-chloro-2-oxo-1,2-
dihydroquinolin-3-yl)-3-phenylprop-2-enamide
a
a
b
c
Rajeev T.Ulahannan , C.Yohannan Panicker *, Hema Tresa Varghese , Robert Musiol , Josef
d
e
f
g
Jampilek , Christian Van Alsenoy , Javeed Ahmad War , Abdulaziz A.Al-Saadi
a
Department of Physics, TKM College of Arts and Science, Kollam, Kerala, India
b
Department of Physics, Fatima Mata National College, Kollam, Kerala, India
c
Institute of Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland.
d
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and
Pharmaceutical Sciences Brno, Palackeho 1/3, 61242 Brno, Czech Republic
e
University of Antwerp, Chemistry Department, Universiteitsplein 1, B2610 Antwerp,
Belgium.
f
Department of Chemistry, Dr.H.S.Gour Central University, Sagar, M.P. 470003, India
g
Department of Chemistry, King Fahd University for Petroleum and Minerals, Dhahran
3
*
1261, Saudi Arabia
author for correspondence: email: cyphyp@rediffmail.com
Phone: 91 9895370968
Abstract
FT-IR and FT-Raman spectra of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-
phenylprop-2-enamide were recorded and analyzed experimentally and theoretically. The
1
synthesis, H-NMR and PES scan results are also discussed. Nonlinear optical behaviour of
the examined molecule was investigated by the determination of first hyperpolarizability. The
calculated HOMO and LUMO energies show the chemical activity of the molecule. The
stability of the molecule arising from hyper-conjugative interaction and charge delocalization
has been analyzed using NBO analysis. From the MEP it is evident that the negative charge
covers the carbonyl group and the positive region is over the NH group. The calculated
geometrical parameters (SDD) are in agreement with that of similar derivatives. Molecular
docking simulations against targets from mycobacterium tuberculosis are reported and the
results suggest that the compound might exhibit inhibitory activity against PknB.
Keywords: DFT; FT-IR; FT-Raman; quinoline; MEP; Molecular docking.
1
. Introduction
Quinoline derivatives have been extensively studied due to their anti-amoebic [1],
anti-viral [2], anti-parasitic [3], anti-malarial [4-10] properties. Quinolines have good electron
mobility, good thermal and oxidative stabilities, high photoluminescence efficiencies and
1

good film forming properties which is important for their use in organic light emitting diodes
OLEDs) [11, 12]. Quinolines are reported to be a promising candidate for the use as
(
PhOLEDs (Phosphorescent Organic Light Emitting diodes) [13] with good nonlinear optical
properties [14, 15]. There has been growing interest in using organic materials for nonlinear
optical devices, functioning as second harmonic generators, frequency converters, electro-
optical modulators, etc. because of the large second order electric susceptibilities of organic
materials. Since the second order electric susceptibility is related to first hyperpolarizability,
the search for organic chromophores with large first hyperpolarizability is fully justified. The
organic compounds showing high hyperpolarizability are those containing an electron
donating group or an electron withdrawing group interacting through a system of conjugated
double bonds. To the best of our knowledge, a detailed description of the spectroscopic
behaviour of the title compound with the help of vibrational spectral techniques and quantum
chemical calculations along with NLO properties has not been given to date. Due to the
different potential biological activity of the title compound, molecular docking of the title
compound is also reported.
2
. Experimental details
General procedure for the preparation of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-
3
-yl)-3-phenylprop-2-enamide
All reagents were purchased from Aldrich. TLC experiments were performed on
alumina-backed silica gel 40 F254 plates (Merck, Darmstadt, Germany). The plates were
illuminated under UV (254 nm) and evaluated in iodine vapour. The melting points were
determined on BoetiusPHMK 05 (VEBKombinatNagema, Radebeul, Germany) and are
uncorrected. Elemental analyses were carried out on an automatic Perkin-Elmer 240
1
microanalyser (Boston, USA). H-NMR spectrum was recorded on a Bruker AM-500 (500
1
MHz for H), Bruker BioSpin Corp., Germany. Chemicals shifts are reported in ppm (δ) to
internal Si(CH
3
4
) , when diffused easily exchangeable signals are omitted. Mass spectra were
measured using a LTQ Orbitrap Hybrid Mass Spectrometer (Thermo Electron Corporation,
USA) with direct injection into an APCI source (400 °C) in the positive mode.
Aniline (5mmol) and malonic acid (5mmol) were thoroughly mixed with 20g PPA
and heated under stirring in microwave reactor at 400W during 2×20 minutes with 5 minutes
interval. The temperature reached 210°C. Then the mixture was poured into crushed ice and
the beige solid was filtered and purified by extraction with EtOH and a white crystalline
compound 4-hydroxyquinolin-2(1H)-one was obtained in yield 35% [16]. 4-Hydroxy-3-
2

nitroquinolin-2(1H)-one was obtained according to the described nitration procedure [17] as a
yellow crystalline compound in yield 71%. Nitro derivative (9.7mmol) and tin powder
(
32mmol) were stirred with 36% HCl (8.1mL). The mixture was warmed at 80-90°C for
0 min. The brown solution was cooled to room temperature and filtered. The filtrate was
alkalized with NH (aq) and warmed for 20 min. Then Celite was added and filtered. The
3
3
solid was washed thoroughly with hot water (80°C). The combined filtrates were
concentrated and acidified. After cooling 3-amino-4-hydroxyquinolin-2(1H)-one as a white
crystalline compound was obtained in yield 85% [16]. 3-Amino-4-chloroquinolin-2(1H)-one
was obtained according to the described chloration procedure with POCl
0 min in acetonitrile [17]. This compound (1mmol) was mixed with water (5mL), Et
5mL) and sodium bicarbonate (0.3g). The resulted mixture was stirred in an ice bath (-3°C)
and 10mL of Et O solution of cinamoyl chloride (1mmol) was added slowly. The resulting
mixture was stirred at ambient temperature for 2 days, cooled in fridge and filtered. Et O was
3 3
, Et N under reflux
3
2
O
(
2
2
added to the solid and dried. A white crystalline compound was obtained (supporting
information: Scheme.1).
The FT-IR spectrum (Fig. 1) was recorded using KBr pellets on a DR/Jasco FT-IR
-
1
6
300 spectrometer. The spectral resolution was 4 cm . The FT-Raman spectrum (Fig. 2) was
obtained on a Bruker RFS 100/s, Germany. For excitation of the spectrum the emission of
Nd:YAG laser was used with excitation wavelength 1064 nm and maximal power 150mW;
measurement were performed on solid samples. One thousand scans were accumulated with a
-
1
total registration time of about 30 min. The spectral resolution after apodization was 2 cm .
3
. Computational details
Calculations of the title compound are carried out with Gaussian09 program [18]
using the HF/6-31G (6D, 7F), B3LYP/6-31G (6D, 7F) and B3LYP/SDD quantum chemical
calculation methods to predict the molecular structure and vibrational wave numbers.
Molecular geometry was fully optimized by Berny’s optimization algorithm using redundant
internal coordinates. Harmonic vibrational wave numbers are calculated using the analytic
second derivatives to confirm the convergence to minima on the potential surface. The wave
number values computed at the Hartree-Fock level contain known systematic errors due to
the negligence of electron correlation. We therefore, have used the scaling factor value of
0
.8929 for HF method. The DFT hybrid B3LYP functional and SDD methods tend to
overestimate the fundamental modes, therefore scaling factor of 0.9613 has to be used for
obtaining a considerably better agreement with experimental data [19]. The Stuttgart/Dresden
3

effective core potential basis set (SDD) was chosen particularly because of its advantage of
doing faster calculations with relatively better accuracy and structures [20, 21]. Then
frequency calculations were employed to confirm the structure as minimum points in energy.
Parameters corresponding to optimized geometry (SDD) of the title compound (Fig. 3) are
given in Table 1. The absence of imaginary wavenumbers on the calculated vibrational
spectrum confirms that the structure deduced corresponds to minimum energy. The
assignments of the calculated wave numbers are aided by the animation option of
GAUSSVIEW program, which gives a visual presentation of the vibrational modes [22]. The
potential energy distribution (PED) is calculated with the help of GAR2PED software
package [23].
4
4
.
Results and discussion
.1
IR and Raman spectra
The observed IR and Raman bands, calculated (scaled) wavenumbers and
assignments are given in Table 2. The N-H stretching vibrations give rise to bands at 3500-
-
1
3
300 cm [24, 25]. According to Roeges the N-H stretching vibration appears strongly and
-1
broadly in the region 3390 ± 60 cm [26]. For the title compound N-H stretching modes are
-1
assigned at 3419 and 3467 cm theoretically (SDD) and a strong band is observed in the IR
-
1
-1
spectrum at 3377 cm . Mary et al. [27] reported a band at 3343 cm in the IR spectrum,
-
1
-1
3
340 cm in Raman spectrum and 3433 cm theoretically as N-H stretching mode. The C-N-
H vibration in which N and H atoms move in opposite direction of carbon atom in the amide
-1
moiety is reported at 1497 cm theoretically, and the C-N-H vibration in which N and H
-1
atoms move in the same direction of carbon atom in the amide group is reported at 1217 cm
-
1
(
DFT) [28-30]. For the title compound the bands at 1490 (IR) and 1474, 1235 cm (SDD) is
assigned as N-H in-plane bending mode. The out-of-plane bending of NH is expected around
-1
-1
6
50 ± 50 cm [26]. In the present case the band at 675 (IR), 666 (Raman) and 668 cm
(
SDD) is assigned as out-of-plane bending of N-H. According to literature, if N-H is a part of
-1
a closed ring the C-N-H deformation band is absent in the region 1510-1500 cm [26, 31].
-1
For the title compound the N11-H12 deformation band is observed at 1383 cm theoretically.
-1
The out-of-plane N-H deformation is theoretically assigned at 728 cm for N-H being a part
-
1
-1
of the ring. Minitha et al. [32] reported δNH at 1300 cm and γNH at 535 cm . The C17-N18
-1
-1
-1
stretching is assigned at 1196 cm (IR), 1199 cm (Raman) and 1187 cm theoretically.
-1
Louran et al. [33] reported a value at 1220 cm for υC-N for poly aniline. In the case of
aromatic amines a strong C-N stretching absorption is observed in the region in 1342-1266
4

-
1
-1
cm [28, 34]. Varghese et al. [35] reported υC-N mode at 1203 cm in the IR spectrum and at
-1
1
208 cm theoretically.
-
1
The band observed at 1595 cm in SDD is assigned as the stretching mode of
C20=O21. According to literature [31] the stretching mode of C=O is expected in the range
-
1
-1
1
850-1550 cm . The in-plane bending mode of C=O is reported in the range 725 ± 95 cm
-
1
[
26]. The C=O out of plane vibration is reported in the region 595 ± 120 cm [26]. The
-1
C
20=O21 deformation bands are assigned at 704 and 514 cm theoretically (SDD).
In the following discussion the mono-substituted and 1,2-disubstituted benzene ring
are labelled as PhII and PhI respectively. The quinoline has been labelled as ring. For 1,2
light/heavy di-substituted benzenes, the C-H stretching modes of the phenyl ring are expected
-1
in the region 3100-3000 cm [26] and for mono-substituted benzenes, these modes are
-1
expected in the region 3105‐3000 cm [26]. For the title compound these modes are observed
-1
-1
-1
at 3168, 3085 cm (IR), 3149 cm (Raman) and in the range 3124-3069 cm (SDD)
theoretically.
-1
The in-plane deformation modes are seen in the range 1300-1240 cm and 1170-
-
1
1
010 cm for 1,2 light/heavy di-substituted benzenes [26] where δC-H vibrations are seen in
-1
-1
the range 1230-1280 cm and 1170-1000 cm for mono-substituted benzenes [26]. For the
-1
-1
title compound these modes are observed at 1248, 1115 cm (IR), 1253, 1114 cm (Raman)
-1
-1
and 1235, 1246, 1163, 1103 cm (SDD) for di-substituted benzenes and at 1071 cm (IR),
-
1
-1
1
177, 1150 cm (Raman), 1328, 1177, 1160, 1068, 1014 cm (SDD) for mono-substituted
-1
benzenes. The out-of-plane C-H deformation bands are expected in the region 995-720 cm
-1
[
26] and 1000-700 cm [26, 30] for the di-substituted and mono-substituted benzenes
-1
-1
respectively. These modes are observed at 865 cm in IR, 944, 862 cm in Raman and 992,
-
1
-1
9
8
57, 868, 771 cm in SDD for the di-substituted benzene and at 937, 792 cm (IR), 1000,
-1
-1
48 cm (Raman) 1000, 985, 929, 848, 774 cm (SDD) for the mono-substituted benzene.
The benzene ring possesses six ring stretching vibrations with sixth is the ring
-1
breathing mode. The υPh modes are expected in the region of 1615‐1270, 1620-1285 cm for
PhI, PhII rings, respectively [26]. Panicker et al., [36] reported this mode in the range of
-
1
1
593‐1011 cm theoretically for PhI, where the ring stretching modes of PhII are reported
-
1
-1
-1
[
36] in the range 1599-1086 cm . The modes at 1449 cm (IR), 1457 cm (Raman) 1593,
-
1
-1
-1
1
1
547, 1445, 1347, 1235 cm (SDD) and 1402 cm (IR) 1585, 1413, 1334 cm (Raman)
-
1
587, 1560, 1469, 1424, 1333 cm (SDD) are assigned as the ring stretching modes of PhI
and PhII, respectively. In ortho di-substitution the ring breathing mode has three wavenumber
5

intervals depending on whether both substituents are heavy, or one of them is heavy, while
-1
the other is light, or both of them are light. In the first case, the interval is 1100-1130 cm , in
-1
-1
the second case 1020-1070 cm , while in the third case it is between 630-780 cm [30]. For
-1
mono-substituted benzenes the ring breathing mode is observed about 1000 cm [26]. For the
-1
-1
-1
title compound the modes at 1030 cm (IR), 1030 cm (Raman) 1022 cm (SDD) and at
-
1
1
3
009 cm (SDD) are assigned as the ring breathing mode for PhI and PhII, respectively.
-1
The C-H stretching outside the ring shows the bands at 3062, 3029 cm (IR), 3067,
-
1
-1
030 cm (Raman) and 3068, 3053 cm (SDD). These bands are expected in the general
-1
region 3000-2840 cm [34]. The in-plane and out-of-plane bending vibrations of the C-H are
-
1
-1
also observed at 1305 cm and 882 cm theoretically and these vibrations are expected in the
-1
-1
regions 1350-1150 cm and 1000-650 cm [26, 34].
The C=C stretching is reported [37] in the IR spectrum around 1610 cm and at 1609
cm in Raman spectrum, where we have assigned this mode at 1606 in IR , 1601 in Raman
-1
-
1
-
1
-1
and 1608 cm in SDD. Arjunan et al. [37] reported the C-C stretching at 1281 and 1334 cm
-1
-1
(
IR) ,1271 and 1384 cm in Raman, where we observed this mode at 1268 and 1305 cm in
SDD, and the latter mode has contributions from other modes too. The C-N stretching is
-1
-1
-1
observed at 1248 cm (IR), 1319, 1253 cm (Raman), 1323, 1246 cm (SDD) while C-N
-1
stretching is reported [37] at 1205 cm . Another C=O stretching mode is theoretically
-
1
observed at 1577 cm which is in agreement with the reported values for similar quinoline
derivatives [38]. For Quinoline ring, C-Cl stretching absorption is observed in the broad
-
1
region between 850 and 550 cm [39, 31]. Arjunan et al. [37] reported C-Cl stretching at 734
-
1
-1
-1
-1
cm (IR), 735 cm (Raman), in-plane bending at 505 cm (IR) 497 cm (Raman) and out-of-
-1
-1
plane at 263 cm where we have assigned these modes at 576, 383, 220 cm theoretically
(
SDD) for the title compound.
In order to investigate the performance of vibrational wavenumbers of the title
compound, root mean square (RMS) values of wavenumbers were calculated using the
ꢐ
ꢂ
ꢃꢄꢂ
ꢑ
ꢊꢋꢌꢊ
ꢍꢎꢏ
expression, RMS = ꢀꢁ ꢅꢆ ꢇꢁꢈ
ꢉ
− ꢈꢉ ꢅ .The RMS error of the observed IR bands and
ꢉ
Raman bands were found to be 28.01 (HF/6-31G(6D,7F)), 31.96 (B3LYP/6-31G(6D,7F)),
2.82 (B3LYP/SDD) and 26.86 (HF/6-31G(6D,7F)), 25.45 (B3LYP/6-31G(6D, 7F)), 9.43
B3LYP/SDD), respectively. The small difference between experimental and calculated
1
(
vibrational modes may be due to the fact that experimental results belong to the solid phase
and theoretical calculations belong to gaseous phase.
6

4
.2
Optimized geometrical parameters
3 4
For the title compound, the computationally obtained bond lengths are, C -C =
1
.3986, C -C
4 5
4 5 6
= 1.4124, C -H10 = 1.088, C -N11 = 1.398, C -C15 = 1.4539, C13-C17 = 1.4828,
C
C
15-Cl16 = 1.8083, C15-C17 = 1.3754, N18-H19 = 1.0194, N18-C20 = 1.4089, C20-O21 = 1.2546,
5
-C =1.4263Å, while the reported values are 1.3806, 1.4211, 1.0841, 1.3725, 1.417, 1.415,
6
1
.7329, 1.375, 1.0161, 1.3826, 1.2538, 1.435Å [36, 38, 40, 41]. The bond lengths of C
5
-N11
(
1.398Å) and C20-N18 (1.4089Å) are shorter than the normal C-N bond length of about 1.48Å.
This points in to the effect of resonance in this part of the molecule [42]. The shortening of
the bond length of C20-O21 (1.2546Å) and C13-O14 (1.2653Å) could be assigned a double bond
character. The longer bond length of C
5
-C (1.4263Å) is due to the delocalization of electron
6
density due to the presence of nearby quinoline ring.
°
°
The observed bond angles are C
4
-C
5
-C
6
= 120.7 , C
1
-C
6
-C
5
= 118.3 , C
1
-C
6
-C15
=
°
°
°
°
°
1
24.1 , C
5
-N11-C13 = 125.3 , N11-C13-C17 = 116.0 , C
6
-C15-Cl16 = 117.6 , C
6
-C15-C17 = 122.1 ,
°
°
°
C
13-C17-C15 = 119.6 , H19-N18-C20 = 116.7 , N18-C20-O21 = 122.6 , while the reported values
°
°
°
°
°
°
°
°
°
°
are 120.2 , 119.5 , 123.6 , 118.6 , 123.6 , 119.5 , 119.7 , 119.2 , 120.6 , 121.4 [36, 38, 40,
°
4
1]. The large bond angle value of C
6
-C15-C17 (122.1 ) is due to the presence of chlorine,
which is highly electronegative and would draw electron density from neighbouring atoms
°
[
43]. The lesser bond angle value of C
1
-C
6
-C
5
(118.3 ) is understood as due to the presence of
°
quinoline ring because for a benzene ring each C-C-C angle is 120 . It is seen that the N11
-
°
°
C
13-O14 bond angle (121.8 ) is considerably greater than the N11-C13-C17 angle (116.0 ),
which is explained as due to a decrease in the repulsion between the lone pairs present in N11
°
and O14 atoms [44]. The dihedral angle H19-N18-C20-O21 is reported as 172.0 [38], while we
°
observe this at -157.0 which denoted a tilting from the plane.
4
.3
Nonlinear optical properties
0
The first hyperpolarizability (β ) of this novel molecular system is calculated using
the SDD method, based on the finite-field approach. In the presence of an applied electric
field, the energy of a system is a function of the electric field. The first hyperpolarizability is
a third-rank tensor that can be described by a 3×3×3 matrix. The 27 components of the 3D
matrix can be reduced to 10 components due to the Kleinman symmetry [45] .The
components of β are defined as the coefficients in the Taylor series expansion of the energy
in the external electric field. When the electric field is weak and homogeneous, this
expansion become
7

1
2
1
6
1
i
E = E − µ F −
i
j
α F F −
i
j
k
β F F F −
i
j
k
l
γ ijkl F F F F + ...
0
∑
i
∑
ij
∑
ijk
∑
24
i
ij
ijk
ijkl
i
where E
0
is the energy of the unperturbed molecule, F is the field at the origin, µ
i
, αij, βijk and
γ
ijkl are the components of dipole moment, polarizability, the first hyperpolarizabilities, and
second hyperpolarizabilities, respectively.
2
2
2 1/2
β
0
= (β
x
+ β
y
+ β )
z
where
β
β
β
x
y
= βxxx+ βxyy+ βxzz
= βyyy+ βxxy+ βyzz
z
= βzzz+ βxxz+ βyyz
-30
The calculated first hyperpolarizability of the title compound is 16.9×10 esu which is 130
-
30
times that of standard NLO material urea (0.13×10 esu) [46]. The first hyperpolarizability
-
30
-30
of quinoline derivatives is reported as 2.24×10 esu and 2.39×10 esu [40, 47]. But
experimental evaluation of this data is not readily available. We conclude that the title
compound is an attractive object for future studies of nonlinear optical properties.
4
.4
HOMO and LUMO
The HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied
Molecular Orbital) are named as frontier molecular orbital (FMO). FMOs play an important
role in optical and electrical properties, as well as in quantum chemistry. The conjugated
molecules are characterized by a HOMO-LUMO separation, which is the result of a
significant degree of intra-molecular charge transfer from the end-capping electron-donor
groups to the efficient electron-acceptor groups through π-conjugated path. The strong charge
transfer interaction through π-conjugated bridge results in substantial ground state donor-
acceptor mixing and the appearance of a charge transfer band in the electronic absorption
spectrum (Fig. 4). The energy gap between the HOMO and LUMO energy is basis for
molecular chemical stability, chemical reactivity and hardness-softness of the molecule [48].
The energy gap is found to be 2.23eV.
4
.5
Molecular Electrostatic Potential
MEP is related to the electron density and is a very useful descriptor in understanding
sites for electrophilic and nucleophilic reactions as well as hydrogen bonding interactions
49, 50]. The electrostatic potential V(r) is also well suited for analyzing processes based on
[
the "recognition" of one molecule by another, as in drug-receptor, and enzyme-substrate
interactions, because it is through their potentials that the two species first "see" each other
8

[
51, 52]. To predict reactive sites of electrophilic and nucleophilic attacks for the investigated
molecule, MEP at the B3LYP/SDD optimized geometry was calculated. The negative (red
and yellow) regions of MEP were related to electrophilic reactivity and the positive (blue)
regions to nucleophilic reactivity (Fig. 5). From the MEP it is evident that the negative charge
covers the carbonyl group and the positive region is over the NH group. The more electro
negativity in the carbonyl group makes it the most reactive part in the molecule.
4
.6. Natural bond orbital analysis
The natural bond orbital (NBO) calculations were performed using NBO 3.1 program
[
53] as implemented in the Gaussian09 package at the B3LYP/SDD level in order to
understand various second-order interactions between the filled orbital of one subsystem and
vacant orbital of another subsystem, which is a measure of the intra-molecular delocalization
or hyper-conjugation. NBO analysis provides the most accurate possible 'natural Lewis
structure' picture of 'j' because all orbital details are mathematically chosen to include the
highest possible percentage of the electron density. A useful aspect of the NBO method is
that it gives information about interactions of both filled and virtual orbital spaces that could
enhance the analysis of intra- and inter-molecular interactions. The second-order Fock-
matrix was carried out to evaluate the donor-acceptor interactions in the NBO basis. The
interactions result in a loss of occupancy from the localized NBO of the idealized Lewis
structure into an empty non- Lewis orbital. For each donor (i) and acceptor (j) the
stabilization energy (E2) associated with the delocalization i → j is determined as
2
(
F )
i, j
E (2) = ∆E = q
ij
i
(
E − E )
j
i
q
i
→donor orbital occupancy, E
i
, E
j
→diagonal elements, Fij →the off diagonal NBO Fock
matrix element.
In NBO analysis large E (2) value shows the intensive interaction between electron-
donors and electron- acceptors, and greater the extent of conjugation of the whole system, the
possible intensive interaction are given in Table 3. The second-order perturbation theory
analysis of Fock-matrix in NBO basis shows strong intra-molecular hyper-conjugative
interactions are formed by orbital overlap between n(Cl), n(O) and π*(C-C), σ*(C-N), bond
orbital which result in ICT causing stabilization of the system. There occurs an intra-
molecular hyper-conjugative interaction of C13-N11 from O14 of n
increases ED(0.06847e) that weakens the respective bonds C13-N11 leading to stabilization of
1.92 kJ/mol. Another hyper-conjugative interaction of C15-C17 from Cl16 of n
(Cl16)→
2
(O14)→ σ*(C13-N11) which
2
2
9

π*(C15-C17) which increases ED (0.29246e) that weakens the respective bonds C15-C17
leading to stabilization of 12.68 kJ/mol. Another strong hyper-conjugative interaction of C20
(O21)→σ*(C20-N18) which increases ED (0.08318e) that weakens the
-
N
18 from O21 of n
2
respective bonds C20-N18 leading to stabilization of 25.5 kJ/mol. These interactions are
observed as an increase in electron density in C-C orbital that weakens the respective bonds.
The increased electron density at the oxygen, nitrogen and chlorine atoms leads to the
elongation of respective bond length and a lowering of the corresponding stretching wave
number. The electron density is transferred from the n(N) to the anti-bonding π* orbital of the
C-C and C-O bonds, and also from n(Cl) to the anti-bonding π* orbital of the C-C explaining
both the elongation and the red shift [54].The hyper-conjugative interaction energy was
deduced from the second-order perturbation approach. Delocalization of electron density
between occupied Lewis-type (bond or lone pair) NBO orbital and formally unoccupied (anti
bond or Rydberg) non-Lewis NBO orbitals corresponds to a stabilizing donor-acceptor
interaction. The NH and C=O stretching modes can be used as a good probe for evaluating
the bonding configuration around the atoms and the electronic distribution in the ring. Hence
the title compound is stabilized by these orbital interactions.
The NBO analysis also describes the bonding in terms of the natural hybrid orbital
n
2
(O14), which occupy a higher energy orbital (-0.26770a.u.) with considerable p-character
99.99%) and low occupation number (1.87789) and the other n (O14) occupy a lower energy
orbital(-0.69816a.u.) with p-character (34.55%) and high occupation number (1.97573). The
NBO analysis also describes the bonding in terms of the natural hybrid orbital n (Cl16), which
occupy a higher energy orbital (-0.31704a.u.) with considerable p-character (99.90%) and
low occupation number (1.92) and the other n (Cl16) occupy a lower energy orbital (-
.32163a.u.) with p-character (99.70%) and high occupation number (1.97019). The NBO
analysis also describes the bonding in terms of the natural hybrid orbital n (O21), which
occupy a higher energy orbital (-0.24881a.u.) with considerable p-character (99.98%) and
low occupation number (1.87847) and the other n (O21) occupy a lower energy orbital (-
.67333a.u.) with p-character (36.17%) and high occupation number (1.97550). Thus, a very
(
1
3
2
0
2
1
0
close to pure p-type lone pair orbital participates in the electron donation to the π*(C13-O14
orbital for n (N11)→π*(C13-O14), σ*(C13-C17) orbital for n
orbital for n (O14)→σ*(C13-N11), σ*(C -C15) orbital for n
orbital for n
(Cl16)→π*(C15-C17) , π*(C20-O21) orbital for n
)
)
)
)
1
1
(O14)→σ*(C13-C17) , σ*(C13-N11
(Cl16)→σ*(C -C15), π*(C15-C17
(N18)→π*(C20-O21), σ*(C20-C22
2
6
1
6
2
1
1
0

orbital for n
the compound. The results are tabulated in Table 4.
.7 Mulliken Charges
The calculation of atomic charges plays an important role in the application of
1
(O21)→σ*(C20-C22), σ*(C20-N18) orbital for n (O21)→σ*(C20-N18)interactions in
2
4
quantum mechanical calculations to molecular systems. Mulliken charges are calculated by
determining the electron population of each atom as defined in the basis of functions. The
charge distributions calculated by the Mulliken [55] and NBO methods for the equilibrium
geometry of the title compound are given in Table 5. The charge distribution on the molecule
has an important influence on the vibrational spectra. In the title compound, the distribution
of Mulliken atomic charge shows the direction of delocalization and shows that the natural
atomic charges are more sensitive to the changes in the molecular structure than Mulliken’s
net charges. Also we have done a comparison of Mulliken charges obtained by different basic
sets and tabulated it in Table 6 in order to assess the sensitivity of the calculated charges to
changes in (i) the choice of the basis set; (ii) the choice of the quantum mechanical method.
The results can, however, better be represented in graphical form as shown in Fig. 6. We have
observed a change in the charge distribution by changing different basis sets. Distribution of
the charges in this compound is also influenced by the C-O moieties. Based on the charge
distribution calculated by various ways (see Tables 5 and 6) it can be concluded that all the
hetero atoms showed significant electron density. An increased electron density (negative
charge) can be also found at C17, C22, N11 and N18. Significantly positive charges were
predicted for C13, and C20. Therefore it can be concluded that electrophilic substitution of the
quinoline scaffold is more preferred than nucleophilic substitution. Reactions based on the
attack of a nucleophile are favoured especially on carbonyl/carboxyl carbons (C13, C20).
4
.8
PES scan studies
For the dihedral angles C15-C17-N18-H19 and C15-C17-N18-C20, a detailed potential
energy surface (PES) scan has been performed at B3LYP/SDD level to reveal all possible
conformations of the title compound. The PES scan was carried out by minimizing the
potential energy in all geometrical parameters by changing the torsion angle at every 10˚ for
1
80˚ rotation around the bond. The results obtained in PES scan study by varying the torsion
perturbation around the above dihedral angles are plotted in Fig. 7 and Fig. 8. For the C15
17-N18-H19 rotation, the minimum energy was obtained at -153.6˚in the potential energy
-
C
curve of energy -1413.7549 Hartrees. For the C15-C17-N18-C20 rotation, the minimum energy
occurs at 51.1˚ in the potential energy curve of energy -1413.7550 Hartrees.
1
1

1
4
.9.
H-NMR spectrum
Using TMS as internal standard, experimental spectrum data of the title compound in
DMSO is obtained at 500 MHz and is shown in Table 7. The absolute isotropic chemical
shielding of the title compound was calculated by B3LYP/GIAO model [56]. Relative
chemical shifts were then estimated by using the corresponding TMS shielding: σcalc(TMS)
calculated in advance at the same theoretical level as this paper. Numerical values of
chemical shift δcalc = σcalc(TMS) - σcalc together with calculated values of σcalc (TMS), are
1
reported in Table 7. The chemical shift and the experimental H-NMR data were in
agreement. Thus, the results have shown that the predicted proton chemical shifts were in
good agreement with the experimental data for the title compound.
4
.10. Molecular docking
Quinolones constitute a series of broad-spectrum antibacterial drugs [57]. Extensive
literature survey reveals that quinole derivatives mostly possess antimicrobial activity [58-
0]. From this background knowledge we decided to evaluate antimicrobial potential of the
6
quinoline derivative. With time most microbs develop resistance against antimicrobial drugs.
This leads to an ever increasing demand for the development of new antimicrobial agents. As
mycobacterium tuberculosis is the leading bacterial infection in the world [61] so we decided
to carry molecular docking simulations against targets from mycobacterium tuberculosis. The
Mycobacterium tuberculosis genome contains 11 serine/threonine kinase genes including
PknA and PknB, which play vital role in cell shape control and cell wall synthesis. PknB, a
receptor-like protein kinase is essential for myco-bacterial viability. PknB is predominant in
many more distantly related gram-positive bacteria [62, 63]. Molecular docking simulations
were performed on AutoDock-Vina software [64]. The 3D crystal structure of M.
tuberculosis PknB was obtained from Protein Data Bank (PDB ID: 2FUM) [65]. The protein
was prepared for docking by removing the co-crystallized ligand, water molecules and co-
factors. Auto Dock Tools (ADT) graphical user interface was used to calculate Kollman
charges and to add polar hydrogen. Ligand was prepared for docking by minimizing its
energy at B3LYP/SDD level of theory. Charges were calculated by Geistenger method.
Active site of the protein was defined so as to include residues of the active site within the
grid size of 40Å×40Å×40Å. The most popular algorithm, Lamarckian Genetic Algorithm
(
LGA) available in Autodock was employed for docking. Docking protocol was tested by
extracting co-crystallized inhibitor from the protein and then docking the same. Docking
protocol which we employed predicted the same conformation as was present in the crystal
1
2

structure with RMSD value well within the reliable range of 2Å. Amongst the docked
conformations, one which binds at the active site with high affinity was visualized for
detailed ligand-protein interactions in Discover Studio Visualizer 4.0 and Pymol software.
The ligand binds at the catalytic site of substrate (Fig. 9) by weak non-covalent interactions
most prominent of which are H-bonding and alkyl-π interactions.Val95 form H-bonds of
2
.68Å length with carbonyl oxygen attached to quinoline ring. Val72, Val25 and Leu17 hold
the aromatic rings by alkyl-π interactions (supporting information Fig.S1). The inhibitor
2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide forms a stable
complex with PknB as is evident from the binding affinity (∆G in kcal/mol) values
supporting material Table S1). These preliminary results suggest that the compound might
(
(
exhibit inhibitory activity against PknB. This may result in development of new anti-
tuberculostic agents. However biological tests need to be done so as to validate the
computational predictions.
5
.
Conclusion
The vibrational spectroscopic studies of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-
3
-yl)-3-phenylprop-2-enamide were reported experimentally and theoretically. Potential
energy distribution of normal modes of vibrations was done using GAR2PED program. The
ring stretching modes in IR and Raman spectra are evidence for charge transfer interaction
between the donor and the acceptor group through the π system. This along with the lowering
of HOMO-LUMO band gap supports for the bioactivity of the molecule. NBO analysis
predicts a strong intra-molecular hyper conjugative interaction of (C13-O14) from N11 of
n
1
n
1
n
1
(N11), (C13-C17) from O14 of n
(Cl16), (C15-C17) from Cl16 of n
(O21), (C20-N18) from O21 of n
1
(O14), (C13-N11) from O14 of n
2
(O14), (C
6
-C15) from Cl16 of
2
(Cl16), (C20-O21) from N18 of n
1
(N18), (C20-C22) from O21 of
2
(O21). MEP predicts the most reactive part in the molecule.
The calculated first hyperpolarizability is comparable with the reported values of similar
derivatives and is an attractive object for future studies in non-linear optics. The minimum
energy surfaces are obtained from the potential energy curve by PES scan studies. In addition
1
the calculated H-NMR results are in good agreement with experimental data. The title
compound,
(2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide
forms a stable complex with PknB as is evident from the binding affinity and molecular
docking studies suggest that the compound might exhibit inhibitory activity against PknB.
Acknowledgements
1
3

The authors are thankful to University of Antwerp for access to the university’s CalcUA
supercomputer cluster. JAW would like to thank Department of Science and Technology,
New Delhi, India for a INSPIRE fellowship and RTU thanks University of Kerala, India for a
research fellowship. A.A.Al-Saadi thanks King Fahd University for Petroleum and Minerals
for providing the computing facility to support this work.
References
[
[
[
1]
2]
3]
F. Hayat, A. Salahuddin, S. Umar, A. Azam, Eur. J. Med. Chem. 45 (2010) 4669-
675.
4
L.M. Bedoya, M.J. Abad, E. Calonge, L.A. Saavedra, C.M. Gutierrez, V.V.
Kouznetsov, J. Alcami, P. Bermejo, Antivir. Res. 87 (2010) 338-344.
A.M. Asiri, A.O. Baglaf, R.M. Abdel-Rahman, S.A. Khan, M. Ishaq, Asian J. Chem.
2
5 (2013) 7779-7782.
[
[
[
[
[
[
[
[
[
4]
5]
6]
7]
8]
9]
J. Zeigler, R. Linck, D.W. Wright, Curr. Med. Chem. 8 (2001) 171-189.
P.M.S. Chauhan, S.K. Srivastava, Curr. Med. Chem. 8 (2001) 1535-1542.
O. Famin, H. Krugliak, H.Ginsberg, Biochem. Pharmacol. 58 (1999) 59-68.
F.M.D. Ismail, M.J. Dascombe, P. Carr, J. Pharm. Pharmacol. 50 (1998) 483-492.
M.L. Go, T.L. Nigam, A.L.C. Tan, Eur. J. Pharm. Sci. 6 (1998) 19-26.
A. Dorn, S.R. Vippagunda, H. Mitile, Biochem. Pharmacol. 55 (1998) 727-736.
10] K. Singh, H. Kaur, K. Chibale, J. Balzarini, Eur. J. Med. Chem.66 (2013) 314-323.
11] C.H. Chen, J.M. Shi, Coord. Chem. Rev. 171 (1998) 161-174.
12] A.P. Kulkarni, J. Tonzola, A. Babel, S.A. Jenekhe, Chem. Mater. 16 (2004) 4556-
4
573.
[
13] J. Park , J.S. Park , Y.G. Park , J.Y. Lee , J.W. Kang, J. Liu, L. Dai, S. Jin, Org.
Electron. 14 (2013) 2114-2123.
[
[
[
14] S. Yamaguchi, M. Goto, H. Takayanagi, H. Ogura, Bull. Chem. Soc. Jpn. 61 (1988)
1
026-1028.
15] P. Zaderenko, M.S. Gel, P. Lopez, P. Ballesteros, I. Fonseco, A. Albert, Acta
Cryst. B53 (1997) 961-967.
16] J. Jampilek, R. Musiol, M. Pesko, K. Kralova, M. Vejsova, J. Carroll, A. Coffey, J.
Finster, D. Tabak, H. Niedbala, V. Kozik, J. Polanski, J. Csollei, J. Dohnal, Molecules
1
4 (2009) 1145-1159.
[
17] V. Dolle, E. Fan, C.H. Nguyen, A. M. Aubertin, A. Kirn, M.L. Andreola, G.
Jamieson, L. Tarrago-Litvak, E. Bisagni, J. Med. Chem. 38 (1995) 4679-4686.
1
4

[
18] Gaussian 09, Revision B.01, M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria,
M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson,
H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng,
J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida,
T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery, Jr., J.E.
Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N.
Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C.
Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E.
Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann,
O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K.
Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich,
A.D. Daniels, O. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski, D.J. Fox, Gaussian,
Inc., Wallingford CT, 2010.
[
19] J.B. Foresman, in: E. Frisch (Ed.), Exploring Chemistry with Electronic Structure
Methods: A Guide to Using Gaussian, Gaussian, Inc., Pittsburg, PA, 1996.
20] P.J. Hay, W.R. Wadt, J. Chem Phys. 82 (1985) 270-283.
[
[
[
21] J. Zhao, Y. Zhang, L. Zhu, J. Mol. Struct. Theochem. 671 (2004) 179-187.
22] GaussView, Version 5, R. Dennington, T. Keith, J. Millam, Semichem Inc., Shawnee
Mission KS, 2009.
[
[
23] J.M.L. Martin, C.V. Alsenoy, GAR2PED, A Program to Obtain a Potential Energy
Distribution from a Gaussian Archive Record, University of Antwerp, Belgium, 2007.
24] L.J. Bellamy, The IR spectra of complex molecules, John Wiley & sons, New York
1
975.
[
[
25] A. Spire, M. Barthes, H. Kallouai, G.D. Nunzio, Physics D 137 (2000) 392-396.
26] N.P.G. Roeges, A guide to the complete interpretation of IR spectra of Organic
Compounds, Wiley, New York 1994.
[
[
27] Y.S. Mary, C.Y. Panicker, H.T. Varghese, K. Raju, T.E. Bolelli, I. Yildiz, M.C.
Granadeiro, H.I.S. Nogueira. J. Mol. Struct 994 (2011) 223-231
28] N.B. Colthup, L.H. Daly, S.E. Wiberly, Inroduction to Infrared and Raman
Spectroscopy, third ed., Academic Press, Boston, 1990.
[
[
29] A.S. El-Shahawy, S.M. Ahmed, N.K. Sayed, Spectrochim. Acta 66 (2007) 143-152.
30] G. Varsanyi, Assignments of Vibrational Spectra of Seven Hundred Benzene
Derivatives, Wiley, New York, 1974.
1
5

[
[
[
[
31] G. Socrates, Infrared Characteristic Group Frequencies, John Wiley and Sons, New
York, 1981.
32] R. Minitha , Y.S. Mary, H.T. Varghese C.Y. Panicker, R. Ravindran, K. Raju, V.M.
Nair, J. Mol. Struct. 985 (2011) 316-322.
33] G. Louran, M. Lapkowski, S. Quillard, A. Pron, J.B. Buisson, S. Lefrant, J. Phys.
Chem. 100 (1996) 6998-7006.
34] R.M. Silverstein, F.X. Webster, Spectrometric Identification of Organic Compounds,
sixth ed., John Wiley, Asia, 2003.
[
35] H.T. Varghese, C.Y. Panicker, D. Philip, P. Pazdera, Spectrochim.Acta 67 (2007)
055-1059.
1
[
36] C.Y. Panicker, H.T. Varghese, K.R. Ambujakshan, S. Mathew, S. Ganguli, A.K.
Nanda, C.V. Alsenoy, Eur. J. Chem. 1 (2010) 37-43.
[
[
37] S. Arjunan, P. Mohan, C.V. Mythili, Spectrochim. Acta 72 (2009) 783-788.
38] S.R. Sheeja, N.A. Mangalam, M.R.P. Kurup, Y.S. Mary, K. Raju , H.T. Varghese, C.
Y. Panicker, J. Mol. Struct. 973 (2010) 36–46.
[
[
39] M. Kurt, M. Yurdakul, S. Yurdakul, J. Mol. Struct. Theochem. 711 (2004) 25-32.
40] A.J. Camargo, H.B. Napolitano, J.Z. Schpector, J. Mol. Struct. (Theochem.) 816
(
2007) 145-151.
41] Y. S. Mary, H. T. Varghese, C.Y. Panicker, M. Dolezal, Spectrochim.Acta 71 (2008)
25-730.
[
7
[
[
42] H. Arslan, U. Florke, N. Kulcu, G. Binzet, Spectrochim. Acta 68 (2007)1347-1355.
43] C.Y. Panicker, H.T. Varghese, V.S. Madhavan, S. Mathew, J. Vinsova, C. Van
Alsenoy, Y.S Mary ,Y.S Mary; J. Raman Spectrosc. 40 (2009) 2176-2186.
44] B.N.B. Raj, M.R.P. Kurup, E. Suresh, Spectrochim. Acta 71 (2008) 1253-1260.
45] D.A. Kleinman, Phys. Rev. 126 (1962) 1977-1979.
[
[
[
[
[
[
[
[
46] M. Adant, M. Dupuis, J.L. Bredas, Int. J. Quantum. Chem. 56 (1995) 497-507.
47] G. Purohit, G.C. Joshi, Indian J. Pure Appl. Phys. 41 (2003) 922-927.
48] D.F.V. Lewis, C. Ioannides, D.V. Parke, Xenobiotica 24 (1994) 401-408.
49] E. Scrocco, J. Tomasi, Adv. Quantum. Chem. 103 (1978) 115-193.
50] F.J. Luque, J.M. Lopez, M. Orozco, Theor. Chem. Acc. 103 (2000) 343-345.
51] P. Politzer, J. S. Murray, in: Theoretical Biochemistry and Molecular Biophysics: A
Comprehensive Survey, Vol. 2, Protein: D.L. Beveridge, R. Lavery, Eds., Adenine
Press, Schenectady, NY, 1991, Chap. 13.
1
6

[
[
52] E. Scrocco, J. Tomasi, Top. Curr. Chem. 42 (1973) 95-170.
53] E.D. Glendening, A.E. Reed, J.E. Carpenter, F. Weinhold, NBO Version 3.1,
Theoretical Chemistry Institute, University of Wisconsin, Madison, CI.
[
[
[
[
[
54] J. Choo, S. Kim, H. Joo, Y. Kwon, J. Mol. Struct. (Theochem.) 587 (2002) 1-8.
55] R.S. Mulliken, J. Chem. Phys., 23 (1955) 1833-1840.
56] K. Wolinski, J.F. Hinton, P. Pulay, J. Am. Chem. Soc. 112 (1990) 8251-8260.
57] M.I. Andersson, A.P. MacGowan, J. Antimicorb. Chemother. 51 (2003) 1-11.
58] R. Wise, J.M. Andrews, J.P. Ashby, R.S. Matthews, Antimicrob. Agents Chemother.
3
2 (1988) 617-622.
[
[
59] H.C. Neu, Annual Rev. Med. 43 (1992) 465-486.
60] M.J. Pucci, J.A. Wiles, Bacterial Topoisomerase Inhibitors: Quinolones and Beyond,
In Antimicrobials, ch.16, pp.307-326, Springer Berlin, Heidelber, 2014.
61] M. Chhabria, P. Shailesh, J. Mitesh Anti-Infect. Agents Med. Chem. 9 (2010) 59-103.
62] C.M. Kang, D.W. Abbott, S.T. Park, C.C. Dascher, L.C. Cantley, R.N. Husson, Genes
Dev. 19 (2005) 1692-1704.
[
[
[
63] P. Fernandez, B. Saint-Joanis, N. Barilone, M. Jackson, B. Gicquel, S.T. Cole, P.M.
Alzari, J. Bacteriol. 188 (2006) 7778-7784.
[
[
64] O. Trott, A. J. Olson, J. Comput. Chem. 31 (2010) 455-461.
65] A. Wehenkel, P. Fernandez, M. Bellinzoni, V. Catherinot, N. Barilone, G. Labesse,
M. Jackson, P.M. Alzari., FEBS Lett. 580 (2006) 3018-3022.
Figure Captions
Fig.1 FT-IR spectrum of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-
enamide
Fig.2 FT-Raman spectrum of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-
phenylprop-2-enamide
Fig.3 Optimized geometry (SDD) of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-
phenylprop-2-enamide
Fig.4 HOMO - LUMO plots of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-
phenylprop-2-enamide
Fig.5 MEP plot of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-
enamide
Fig.6. Comparison of different methods for calculated Mulliken charges
Fig.7. Profile of potential energy scans for the torsion angle C15-C17-N18-H19
1
7

Fig.8. Profile of potential energy scans for the torsion angle C15-C17-N18-C20
Fig.9 The docked conformation of the ligand binds at the catalytic site of PnkB. H bonds,
sulphur-π and alkyl-π interactions are represented by green, brown and violet dotted lines,
respectively. Hydrogen bonding pocket is shown for clarity
1
8

1
9

2
1

2
2

2
3

2
4

2
5

2
6

2
7

2
8

2
9

Table(s)
Table 1.Optimized geometrical parameters (B3LYP/SDD) of (2E)-N-(4-chloro-2-oxo-1,2-
dihydroquinolin-3-yl)-3-phenylprop-2-enamide, atom labeling according to Fig.3.
Bond lengths(Å)
Bond angles(°)
Dihedral angles(°)
C1-C2
1.3976
1.4183
1.0845
1.4156
1.0861
1.3986
1.0867
1.4124
1.0880
1.4263
1.3980
1.4539
1.0164
1.3861
1.2653
1.4828
1.8083
1.3754
1.4037
1.0194
1.4089
1.2546
1.485
C2-C1-C6
120.9
120.2
118.9
120.1
119.9
119.9
120.1
120.1
119.8
119.8
120.5
119.7
120.7
120.5
118.8
118.3
124.1
117.7
119.4
125.3
115.3
121.8
116.0
122.1
117.6
122.1
0.0
C6-C1-C2-C3
C6-C1-C2-H8
H7-C1-C2-C3
H7-C1-C2-H8
C2-C1-C6-C5
-0.1
C1-C6
C2-C1-H7
179.8
-179.8
0.1
C1-H7
C6-C1-H7
C2-C3
C1-C2-C3
C2-H8
C1-C2-H8
0.2
C3-C4
C3-C2-H8
C2-C1-C6-C15 -180.0
H7-C1-C6-C5 179.9
H7-C1-C6-C15 -0.2
C3-H9
C2-C3-C4
C4-C5
C2-C3-H9
C4-H10
C5-C6
C4-C3-H9
C1-C2-C3-C4
C1-C2-C3-H9
H8-C2-C3-C4
H8-C2-C3-H9
C2-C3-C4-C5
-0.1
C3-C4-C5
179.9
-179.9
0.1
C5-N11
C6-C15
N11-H12
N11-C13
C13-O14
C13-C17
C15-Cl16
C15=C17
C17-N18
N18-H19
N18-C20
C20=O21
C20-C22
C22-H23
C22=C24
C24-H25
C24-C26
C26-C27
C26-C28
C27-H29
C27-C31
C3-C4-H10
C5-C4-H10
C4-C5-C6
0.0
C4-C5-N11
C6-C5-N11
C1-C6-C5
C2-C3-C4-H10 -179.9
H9-C3-C4-C5 -179.9
H9-C3-C4-H10 0.1
C3-C4-C5-C6 0.1
C1-C6-C15
C5-C6-C15
C5-N11-H12
C5-N11-C13
H12-N11-C13
N11-C13-O14
N11-C13-C17
O14=C13-C17
C6-C15-Cl16
C6-C15=C17
Cl16-C15=C17
C13-C17=C15
C13-C17-N18
C15=C17-N18
C17-N18-H19
C3-C4-C5-N11 -178.9
H10-C4-C5-C6 -179.9
H10-C4-C5-N11 1.1
C4-C5-C6-C1
C4-C5-C6-C15
N11-C5-C6-C1
-0.3
179.9
178.8
1.0884
1.3579
1.091
N11-C5-C6-C15 -1.0
C4-C5-N11-H12 1.9
C4-C5-N11-C13 -178.0
C6-C5-N11-H12 -177.1
C6-C5-N11-C13 2.9
C1-C6-C15-Cl16 -7.2
C1-C6-C15-C17 175.5
C5-C6-C15-Cl16 172.6
1.4697
1.4195
1.4177
1.0869
1.4024
119.6
112.7
127.5
112.8
1